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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

Published on: May 2, 2018

The CTX-M beta-lactamase pandemic

Rafael Cantón1, Teresa M Coque

  • 1Servicio de Microbiología, Hospital Ramón y Cajal, 28034-Madrid, Spain.

Current Opinion in Microbiology
|September 1, 2006
PubMed

Insights

Insertion sequences ISEcp1 and ISCR1 mobilize CTX-M beta-lactamase genes, driving their spread via plasmids. Co-selection with other resistance genes in Escherichia coli facilitates this global pandemic of extended-spectrum beta-lactamases.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • CTX-M enzymes are the leading cause of extended-spectrum beta-lactamase resistance in healthcare and community settings.
  • Insertion sequences (ISs) ISEcp1 and ISCR1 are implicated in the mobilization of beta-lactamase genes from Kluyvera species, showing high homology to blaCTX-Ms.
  • These ISs exhibit specific gene associations: ISEcp1 with most blaCTX-Ms, and ISCR1 with blaCTX-M-2 or blaCTX-M-9.

Purpose of the Study:

  • To investigate the mechanisms and genetic structures facilitating the widespread dissemination of CTX-M extended-spectrum beta-lactamases.
  • To understand the role of insertion sequences and mobile genetic elements in the evolution and spread of CTX-M-producing bacteria.

Main Methods:

  • Analysis of genetic structures, including insertion sequences (ISEcp1, ISCR1), integrons, and transposons, associated with blaCTX-M genes.
  • Plasmid analysis to identify host-range, incompatibility groups, and co-resistance genes.
  • Phylogenetic and genotypic analysis of Escherichia coli isolates carrying CTX-M genes.

Main Results:

  • blaCTX-M genes linked to ISEcp1 are often found in multidrug resistance regions, while those linked to ISCR1 are embedded in class 1 integrons and associated with Tn21-like transposons.
  • These genetic structures are located on plasmids that frequently co-harbor resistance genes for aminoglycosides, tetracyclines, sulfonamides, and fluoroquinolones (qnr, aac(6')-Ib-cr).
  • Dissemination is further driven by specific clones and epidemic strains of Escherichia coli, such as CTX-M-15 producers.

Conclusions:

  • The mobilization by ISEcp1 and ISCR1, coupled with co-selection on mobile genetic elements and plasmids, has significantly contributed to the current pandemic of CTX-M beta-lactamases.
  • Understanding these genetic dissemination pathways is crucial for combating the spread of antibiotic resistance.

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